Christopher Douse

Early career group leaders We appoint researchers from across biology and biomedicine to set up their first groups at the Crick.

The @crick.ac.uk is recruiting Early Career Group Leaders

- Lab set-up, research costs, salaries for up to 5 researchers
- Support for up to 12 years
- Access to our core facilities
- Competitive salary
- Fantastic colleagues
- All areas of biology

Deadline 27 Nov

www.crick.ac.uk/careers-stud...

⚡⚡Excited to announce I'll be starting my lab at the Max Planck Institute of Molecular Genetics (@molgen.mpg.de) in Berlin in December! Leaving sunny California to join a fantastic environment with colleagues who do super cool work.
🔬🦠I'm hiring at all levels! 🔬🦠Check: www.molgen.mpg.de/fueyo-lab

Well done!!!

DNA methylation influences human centromere positioning and function - Nature Genetics Genome-wide and targeted perturbation of DNA methylation at centromeres affects CENP-A positioning and centromere structure, resulting in aneuploidy and reduced cell viability.

#1 Centromeres are epigenetic loci defined by CENP-A, positioned in unmethylated DNA flanked by highly methylated regions. Our work, published in @natgenet.nature.com in collaboration with @naltemose.bsky.social investigates the role of DNAme at human centromeres www.nature.com/articles/s41...

LINE-1 retrotransposons mediate cis-acting transcriptional control in human pluripotent stem cells and regulate early brain development Adami et al. demonstrate that evolutionarily young L1s are expressed in human pluripotent stem cells and are dynamically regulated throughout neural differentiation. The study examines the role of L1s...

New paper from our lab! We found that LINE-1 transposons contribute to early human brain development.

Funded by @asapresearch.parkinsonsroadmap.org

www.cell.com/cell-genomic...

Cities reachable by train from Vienna in under 10 hours

Civilization, visualized

Positively mesmerizing: www.chronotrains.com/en/explore/2...

Complex genetic variation in nearly complete human genomes - Nature Using sequencing and haplotype-resolved assembly of 65 diverse human genomes, complex regions including the major histocompatibility complex and centromeres are analysed.

Nature research paper: Complex genetic variation in nearly complete human genomes

go.nature.com/44YuyIV

Long-read RNA sequencing of transposable elements from single cells using CELLO-seq - Nature Protocols Single-cell long-read RNA sequencing enables the high-fidelity mapping of single-cell expression data from highly sequence-similar transposable elements to unique genomic loci by correcting errors fro...

Very happy to share our protocols paper for CELLO-seq. This will make single cell long read RNA-seq more accessible and provides analysis guidelines. We hope this helps the #transposon #TEsky community and folks working on #singleCell isoform and allelic #gene expression. doi.org/10.1038/s415...

A must read!

We are looking for new colleagues to come join us in Galway as group leaders (Junior and Senior). The Centre for Chromosome Biology is a great place and it is a good time to join. Please reach out if you want to chat about the opportunity!
www.nature.com/naturecareer...

Enhancer adoption by an LTR retrotransposon generates viral-like particles, causing developmental limb phenotypes - Nature Genetics Activation of an LTR retrotransposon inserted upstream of the Fgf8 gene produces viral-like particles in the mouse developing limb, triggering apoptosis and causing limb malformation. This phenotype c...

Finally out! 🥳 Our paper showing how a transposable element (TE) insertion can cause developmental phenotypes is now published @natgenet.nature.com 🧬🦠🐁
Below is a brief description of the major findings. Check the full version of the paper for more details: www.nature.com/articles/s41588-025-02248-5

The work was led by my inspiring PhD student Fereshteh Dorazehi and ably supported by a team of wonderful scientists over many years! Fereshteh and I have presented/will present the story at some recent and upcoming meetings and are happy to hear feedback. For now it's time for summer holidays! 9/9

Second, the factor directing human L1 methylation in early development was unknown - a deletion in the ancestral promoter is thought to evade silencing by the KRAB-ZNF/TRIM28 system. We show MORC2 is critical here, at least for those most dangerous elements transcribed in the pluripotent state. 8/X

First, MORC2 ATPase mutations cause severe developmental disorders: we explain how ATPase activity is coupled to chromatin binding and CpG methylation patterning of different targets. That many of the hyperrepressed genes encode KRAB-ZNFs, themselves TE silencers, is conceptually fascinating! 7/X

Apart from relating human genetic L1 activation to a clear cellular phenotype in development cell models, we are excited about these results for two main reasons...

6/X

Genetic loss of L1 silencing due to MORC2 mutation had severe consequences on cellular fitness in a 2D NPC model after pluripotency exit - rescued upon L1 CRISPRi! (shout out to @anitaada.bsky.social @jakobssonlab.bsky.social for the vector - see www.biorxiv.org/content/10.1... ) 5/X

Explaining the persistence of these transcriptional phenotypes we found striking loss of CpG methylation over the youngest human- and hominoid specific L1s (including polymorphic alleles), and hypermethylation of gene promoters. 4/X

Modelling these effects in pluripotent stem cells, we observed loss of function (transcriptional activation) at L1s and gain of function (transcriptional repression) at promoters, an effect which persisted upon differentiation to neural progenitors. 3/X

We engineered mutations to figure out requirements of MORC2 binding to its distinct chromatin targets. Accumulation of MORC2 at L1s and other broad targets requires reversible ATP-dependent dimerization, whereas engagement of gene promoters does not. Mutation misdirects MORC2 onto promoters. 2/X

MORC2 directs transcription-dependent CpG methylation of human LINE-1 transposons in early neurodevelopment Methylation of CpG dinucleotides is essential for silencing genomic repeats such as LINE-1 retrotransposons (L1s) in the germline and soma. Evolutionarily-young L1s are transcribed in human pluripoten...

Very proud of this work where we define how the MORC2 ATPase directs CpG methylation of active human L1 transposons in early development.

Thanks to co-authors, funders & wonderful environment @lundstem.bsky.social

www.biorxiv.org/content/10.1...

Brief thread below (do people still do that?) 1/X

Transcriptional and post-transcriptional regulation of transposable elements and their roles in development and disease - Nature Reviews Molecular Cell Biology Transposable elements (TEs) comprise nearly half of the human genome. This Review discusses transcriptional and post-transcriptional mechanisms that repress TE activity, how TEs escape this suppressio...

We wrote a review on Transposable Elements (TEs) and almost all aspects of TE silencing and their roles in biological processes & disease.
www.nature.com/articles/s41...

A major KI initiative to recruit new assistant professors with outstanding proposals in all areas of medicine, biomedicine and public health. We offer an amazing research environment, great colleagues and generous startup packages. Check it out and get working on your applications! (repost please!)

Lund University is offering 2-year visiting professorships (20% time) for full professors, with a deadline of August 17. Women are encouraged to apply. More info: https://lu.varbi.com/en/what:job/jobID:835541/ #job

The call just opened!

ki.se/en/about-ki/...

You can apply to several departments simultaneously, check out which depts better fit your profile! Here is the call for our Department of Medical Biochemistry and Biophysics

ki.varbi.com/what:job/job...

Hi, we did this at journal club last week and thought it was brilliant. Congrats!!

Conservation of regulatory elements with highly diverged sequences across large evolutionary distances - Nature Genetics Combining functional genomic data from mouse and chicken with a synteny-based strategy identifies positionally conserved cis-regulatory elements in the absence of direct sequence conservation.

📢 ONLINE @natgenet.nature.com

📰 Conservation of regulatory elements with highly diverged sequences across large evolutionary distances.

By Mike Phan, @danielibrahim.bsky.social and colleagues.

⬇️

www.nature.com/articles/s41...

Conservation of regulatory elements with highly diverged sequences across large evolutionary distances Nature Genetics - Combining functional genomic data from mouse and chicken with a synteny-based strategy identifies positionally conserved cis-regulatory elements in the absence of direct sequence...

How to find Evolutionary Conserved Enhancers in 2025? 🐣-🐭
Check out our paper - fresh off the press!!!
We find widespread functional conservation of enhancers in absence of sequence homology
Including: a bioinformatic tool to map sequence-diverged enhancers!
rdcu.be/enVDN
github.com/tobiaszehnde...

Awful news, I’m really sorry to hear that.

Stem cells as role models for reprogramming and repair Stem cells are a promising source for cellular therapies across many diseases and tissues. Their inherent ability to differentiate into other cell types has been the focus of investigation over decade...

Stem cells as role models for reprogramming and repair | Science www.science.org/doi/10.1126/...

I am looking for postdocs to join my group at NIH. Are you interested in Development, Evolution, Genetics, Genomics, and Human health? Please apply! www.training.nih.gov/jobs/pdf-mb-...